High Risk For Vascular Events Research Articles

Long-Term Outcomes in Patients With Spontaneous Cerebellar Hemorrhage: An International Cohort Study.

Spontaneous intracerebral hemorrhage (ICH) in the cerebellum has a poor short-term prognosis, whereas data on the long-term case fatality and recurrent vascular events are sparse. Herewith, we aimed to assess the long-term case fatality and recurrence rate of vascular events after a first cerebellar ICH. In this international cohort study, we included patients from 10 hospitals (the United States and Europe from 1997 to 2017) aged ≥18 years with a first spontaneous cerebellar ICH who were discharged alive. Data on long-term case fatality and recurrence of vascular events (recurrent ICH [supratentoria or infratentorial], ischemic stroke, myocardial infarction, or major vascular surgery) were collected for survival analysis and absolute event rate calculation. We included 405 patients with cerebellar ICH (mean age [SD], 72 [13] years, 49% female). The median survival time was 67 months (interquartile range, 23-100 months), with a cumulative survival rate of 34% at 10-year follow-up (median follow-up time per center ranged: 15-80 months). In the 347 patients with data on vascular events 92 events occurred in 78 patients, after initial cerebellar ICH: 31 (8.9%) patients had a recurrent ICH (absolute event rate, 1.8 per 100 patient-years [95% CI, 1.2-2.6]), 39 (11%) had an ischemic stroke (absolute event rate, 2.3 [95% CI, 1.6-3.2]), 13 (3.7%) had a myocardial infarction (absolute event rate, 0.8 [95% CI, 0.4-1.3]), and 5 (1.4%) underwent major vascular surgery (absolute event rate, 0.3 [95% CI, 0.1-0.7]). The median time to a first vascular event during follow-up was 27 months (interquartile range, 8.7-50 months), with a cumulative hazard of 47% at 10 years. The long-term prognosis of patients who survive a first spontaneous cerebellar ICH is poor and comparable to that of patients who survive a first supratentorial ICH. Further identification of patients at high risk of vascular events following the initial cerebellar ICH is needed. Including patients with cerebellar ICH in randomized controlled trials on secondary prevention of patients with ICH is warranted.

Ultrasound assessment of the nose vasculature: A review of the common method of non-surgical filler-based rhinoplasty.

With the increasing use of dermal injectable fillers in aesthetic medicine, the popularity of non-surgical filler-based rhinoplasty (NSR) is also growing. While performing this procedure might result in certain vascular complications, injecting deep into the midline of the nose is commonly considered the safest method for blind primary NSR. In this study, we challenged the common NSR method with a Doppler ultrasound study of the nose. The vascular pattern of the common zones of the NSR procedure(radix and nasal tip) of 21 Iranian women were investigated by using a 14 MHz Doppler handheld ultrasound device (Silarious L14PS). Participants had never undergone any procedure on their nose. We focused on the depth of midline vessels in the radix and nasal tip. The radix was studied sagittally and horizontally, and the nasal tip was examined axially by ultrasound. In the radix of eight cases (38%), at least one vessel was observed at midline, and all were superficial. In the nose tip of 18 cases (86%), at least one vessel was observed at midline, and 9 out of these 18 vessels (50%) were deep. As a result, conducting NSR by the common method in our study population was relatively safe in the radix, but there was an increased likelihood of vascular events in the tip. Our research results show that while the common method of the NSR may carry a high risk of vascular events, the safety of this procedure could be enhanced by using ultrasound for planning and conducting a tailored treatment.

The role of intracranial artery calcification (IAC) in stroke subtype and risk of vascular events

ObjectiveTo test the hypothesis that intracranial arterial calcification (IAC) is associated with intracranial large artery stenosis (ILAS) and a higher risk of vascular events and mortality. MethodWe leveraged data from two cohorts, the New York-Presbyterian Hospital/Columbia University Irving Medical Center Stroke Registry Study (NYP/CUIMC-SRS) and the Northern Manhattan Study (NOMAS) to test our hypotheses. We measured IAC using CT scans of participants in both cohorts and expressed IAC as present (vs not) and in tertiles. For the CUIMC-SRS, demographic, clinical and ILAS status was collected retrospectively. In NOMAS, we used research brain MRI and MRA to define asymptomatic ILAS and covert brain infarcts(CBI). We built models adjusted for demographics and vascular risk factors for cross-sectional and longitudinal analyses. ResultsCross-sectionally, IAC was associated with ILAS in both cohorts (OR 1.78, 95% CI: 1.16-2.73 for ILAS-related stroke in the NYP/CUIMC-SRS and OR 3.07, 95%CI 1.13-8.35 for ILAS-related covert brain infarcts in NOMAS). In a meta-analysis of both cohorts, IAC in the upper (HR 1.25, 95%CI 1.01-1.55) and middle tertile (HR 1.27, 95%CI 1.01-1.59) was associated with higher mortality compared with participants with no IAC. There were no longitudinal associations between IAC and risk of stroke or other vascular events. ConclusionIn these multiethnic populations, IAC is associated with symptomatic and asymptomatic ILAS as well as higher mortality. IAC may be a useful marker of higher mortality, the role of IAC as an imaging marker of risk of stroke is less certain.

Efficacy and Safety of Long-Term Ropeginterferon Alfa-2b Treatment in Patients with Low-Risk and High-Risk Polycythemia Vera (PV)

Introduction: Patients with "low-risk” (LR) PV are managed conservatively despite higher risk of vascular events and impaired quality of life compared to a population without PV. Acknowledging new evidence (LOW-PV study, Barbui et al 2021), recent treatment guidelines (European LeukemiaNet [ELN] 2021) recommend ropeginterferon alfa-2b (BESREMi®) as a cytoreductive treatment in LR PV patients meeting specific criteria as well as in high-risk (HR) PV patients. Final data from the phase 3 PROUD-PV and CONTINUATION-PV trials (NCT01949805; NCT02218047) demonstrated the long-term efficacy and safety of ropeginterferon alfa-2b compared with hydroxyurea/best available treatment (HU/BAT); here we report results in the ropeginterferon alfa-2b arm by risk stratum. Methods: PV patients were randomized 1:1 and received ropeginterferon alfa-2b or HU/BAT for ≥6 years. In the ropeginterferon alfa-2b arm, subgroup analyses were performed post-hoc by risk stratum (LR: age ≤60 years and no history of thrombosis; all others HR). Complete hematologic response (CHemR) and molecular response defined by modified ELN criteria were assessed in the full analysis set for CONTINUATION-PV (N=95); safety analyses included all data regardless of roll-over (N=127). Results: CONTINUATION-PV enrolled 46 LR and 49 HR patients in the ropeginterferon alfa-2b arm. At baseline, mean age was 50.7 vs 63.7 years respectively, and median duration since PV diagnosis was 1.9 months vs 1.5 months. HR patients had higher platelet and leukocyte counts at baseline and more frequently presented with clinically significant splenomegaly or PV-related symptoms. Median JAK2V617F allele burden was similar for LR and HR patients (37.0% vs 39.4%), however LR patients were less likely to harbor additional non-driver mutations (11.4% vs 24.4%). The median 4-weekly ropeginterferon alfa-2b dose was comparable in LR and HR patients throughout the study (in the 6th year, 499 µg and 489µg respectively) as was the use of an extended 3-4 weekly dose regimen (6th year: 59.5% vs 65.4%). LR patients achieved a significantly higher CHemR rate than HR patients during long-term treatment (Month 72: 73.2% vs 38.3% in LR and HR respectively [RR: 2.41; 95% CI: 1.50 to 3.90; p=0.0003]). Higher CHemR among LR patients was confirmed in a sensitivity analysis including discontinued patients (last observation carried forward [LOCF]; 80.4% in LR vs 65.3% in HR patients at Month 72) indicating that in the HR group, more patients discontinued despite CHemR. In general, discontinued patients were older than those who completed the study (mean age 62.8 years vs 55.2 years) but did not have a longer duration of PV or markedly greater symptom burden at baseline. Importantly, regardless of risk stratum, most patients receiving ropeginterferon alfa-2b did not require any phlebotomy for the entire 6th year (85.7% of LR patients and 75.0% of HR patients entering the 6th year [p=0.3]). LR patients had a higher molecular response rate than HR patients (LOCF at Month 72: 84.4% vs 49.0% respectively, RR: 2.15 [95% CI: 1.37 to 3.37]; p=0.0009) and achieved molecular response more rapidly (median time to first response: 12 months [95% CI: 12 to 18] vs 18 months [95% CI: 12 to 24]; Log-rank test p=0.03). The median JAK2V617F allele burden was 5.6% for LR and 17.9% for HR patients at Month 72 (p<0.0001). During the entire PROUD-PV/CONTINUATION-PV studies (≥6 years exposure), adverse drug reactions (ADRs) to ropeginterferon alfa-2b led to withdrawal of treatment in 1 (1.8%) LR patient (due to sarcoidosis), and in 13 (18.3%) HR patients (due to thrombocytopenia [n=1], elevated transaminases [n=1], psychiatric disorders [n=2], autoimmune disorders [n=6], hypothyroidism [n=2] and dyspnea/pneumonitis [n=1]). LR patients were also less likely than HR patients to experience ADRS of grade ≥3 severity (5.4% vs 23.9%). Conclusion: These results demonstrate the benefit of ropeginterferon alfa-2b therapy in both HR and LR patient populations. LR patients may have a greater potential benefit: higher hematologic and molecular response rates can be safely achieved, and the patients are more likely to remain on long-term treatment. These data provide further evidence for an early treatment start as recently outlined by the updated ELN guidelines.

Antiphospholipid antibody positivity in early systemic lupus erythematosus is associated with subsequent vascular events.

aPL are found in the blood of 20-30% of patients with SLE. Although aPL cause vascular thrombosis in the antiphospholipid syndrome, it is not clear whether positive aPL levels in early SLE increase risk of subsequent vascular events (VE). In a previous analysis of 276 patients with SLE, we found that early positivity for ≥2 of IgG anti-cardiolipin (anti-CL), IgG anti-β2-glycoprotein I (anti-β2GPI) and anti-domain I of β2-glycoprotein I (anti-DI) showed a possible association with VE. Here we have extended that analysis. Serum samples taken from 501 patients with SLE early in their disease had been tested for IgG anti-CL, anti-β2GPI and anti-DI by ELISA. Complete VE history was available for 423 patients of whom 23 were excluded because VE occurred before the diagnosis of SLE. For the remaining 400 patients we carried out Kaplan-Meier survival analysis to define groups at higher risk of VE. Of 400 patients, 154 (38.5%) were positive for one or more aPL, 27 (6.8%) were double/triple-positive and 127 (31.8%) were single-positive. There were 91 VE in 77 patients, of whom 42 were aPL-positive in early disease. VE were significantly increased in aPL-positive vs aPL-negative patients (P = 0.041) and in double/triple-positive vs single-positive vs aPL-negative patients (P = 0.0057). Omission of the IgG anti-DI assay would have missed 14 double/triple-positive patients of whom six had VE. Double/triple-positivity for IgG anti-CL, anti-β2GPI and anti-DI in early SLE identifies a population at higher risk of subsequent VE.

Prognostic Role of Hypertriglyceridemia in Patients With Stroke of Atherothrombotic Origin.

Hypertriglyceridemia is perceived to promote atherosclerotic pathology, but its role in stroke has not been well defined. Our aim was to assess the contribution of hypertriglyceridemia to residual vascular risk in patients with atherothrombotic stroke. The Tokyo Women's Medical University Stroke Registry is an ongoing prospective, observational registry in which 870 patients with acute ischemic stroke or TIA within 1 week of onset were consecutively enrolled and followed up for 1 year. Hypertriglyceridemia was defined as serum triglycerides levels of ≥150 mg/dL under fasting conditions. Significant stenosis of the cervicocephalic arteries was defined as having ≥50% stenosis or occlusion. The primary outcome was major adverse cardiovascular events, including nonfatal stroke, nonfatal acute coronary syndrome, and vascular death. Of 870 patients (mean age 70.1 years, male 60.9%), 217 (24.9%) had hypertriglyceridemia. High triglycerides levels were significantly associated with an increased prevalence of intracranial artery stenosis, particularly in the anterior circulation, rather than extracranial artery stenosis. Patients with hypertriglyceridemia had a greater risk of major adverse cardiovascular events than those without (annual rate 20.9% vs 9.7%; p < 0.001), even after adjustment for potential confounders, including baseline low-density lipoprotein cholesterol and statin use (adjusted hazard ratio 2.46, 95% CI 1.62-3.74). The higher risk of vascular events in patients with hypertriglyceridemia vs without hypertriglyceridemia was observed among patients with stroke of atherothrombotic origin (n = 174, annual rate 35.1% vs 14.2%; p = 0.001), those with significant intracranial artery stenosis (n = 247, annual rate 29.9% vs 14.7%; p = 0.006), and those with significant extracranial carotid artery stenosis (n = 123, annual rate 23.0% vs 9.4%; p = 0.042). In contrast, hypertriglyceridemia was not predictive of recurrent vascular events in patients with cardioembolic stroke (n = 221, annual rate 19.1% vs 10.5%; p = 0.18). Hypertriglyceridemia is an important modifiable risk factor that drives residual vascular risk in patients with stroke of atherothrombotic origin, even while on statin therapy. UMIN000031913 at upload.umin.ac.jp. This study provides Class I evidence that in patients with atherothrombotic stroke, hypertriglyceridemia is associated with an increased risk of major cardiovascular events.

Description of a safe doppler ultrasound-guided technique for hyaluronic acid filler in the face-A method to avoid adverse vascular events.

Knowledge of facial anatomy is essential for professionals intending to inject hyaluronic acid (HA) into that region, but due to the considerable anatomical variations in region, it does not guarantee the complete safety of the procedure. Similarly, procedures widely disseminated among professionals, such as aspiration and the use of cannulas, do not ensure total safety against vascular occlusion events caused by the filler. This article describes a technique for injecting hyaluronic acid into the face guided by Doppler ultrasonography (DUS) in order to ensure greater safety against vascular occlusion events secondary to the procedure. We describe a Doppler ultrasound-guided filling technique, with an 18MHZ transducer, consisting of three steps: arterial mapping, real-time ultrasound-guided filling, and assessing the perfusion. The described technique was performed in 480 patients and can be adopted in the routine of professionals who inject hyaluronic acid, especially in areas at high risk for vascular events. Its use results in greater safety against vascular occlusion events secondary to the procedure, without the need for prior aspiration. We conclude that there is a local vasodilation right after the filling that makes it difficult the possibility of extrinsic compression exerted by the filler on the vessel. Furthermore, the product moves to deep planes even with the bevel facing up (toward the epidermis). We believe that in the future the use of Doppler ultrasound-guided filling technique will be mandatory for professionals who intend to perform HA injection, to both ensure patient safety and provide legal protection for the professional.

Abstract P652: Burden of Vascular Events Amongst TIA Patients - A Nationwide Estimate

Introduction: Literature reported, 9-17% transient ischemic attack (TIA) patients have a vascular event within 90 days but there is limited data on long term risk involvement of vascular events following TIA. Aim: To identify prevalence and association of cardiovascular diseases (CVD) and cerebrovascular disorders (CeVD) amongst early and late TIA. Methods: We performed a retrospective cross-sectional analysis of Nationwide Inpatient Sample (2016-2017) in adults hospitalizations. Early TIA (primary diagnosis), late TIA (secondary diagnosis-within a year) and vascular events [CVD (AFib, IHD, acute MI angina) and CeVD (AIS, ICeH, SAH)] amongst TIA were identified using ICD 10 CM codes. Prevalence of vascular events were compared amongst patients with TIA and without TIA. Weighted analysis to account for sampling strategy using mix-effect multivariable survey logistic regression was performed to evaluate odds of having vascular events amongst TIA in comparison to non-TIA. Results: Amongst 58,259,589 US hospitalizations, 0.38% and 5.92% patients had early and late TIA, respectively. Patients with late TIA had higher prevalence of acute MI (4.9 vs 0.5 vs 3.4%), IHD (44 vs 28.6 vs 20.6%), angina (0.3 vs 0.2 vs 0.2%), AFib (22 vs 15.3 vs 10.9%), AIS (5.3 vs 0.6 vs 2%), SAH (0.2 vs 0.03 vs 0.1%) and ICeH (0.8 vs 0.04 vs 0.4%) compared to early TIA and no-TIA, respectively. (p&lt;.0001) Patients with late TIA had 23% higher risk of having Afib [aOR 1.23; 95%CI 1.22-1.23] and higher odds of having IHD [1.52; 1.52-1.53], AIS [1.72; 1.70-1.74], and ICeH [1.29; 1.25-1.33]. (Table 1) Conclusion: We found a higher prevalence of late TIA amongst US hospitalizations. Additionally, late TIA patients had a higher risk of vascular events like Afib, IHD, and stroke. Hence, a thorough clinical investigation and long term followup of TIA patients may mitigate the risk of future vascular events and associated health care burden.

Cervical Carotid Artery Dolichoectasia as a Marker of Increased Vascular Risk.

Cervical carotid artery (cCA) dolichoectasia (DE) is characterized by elongation, tortuosity, and/or dilatation. The prevalence of cCA DE has been reported 13-31% in population-based and 14-58% in hospital-based studies. The exact mechanisms of this aberrant arterial remodeling are unknown. Although atherosclerosis has often been implicated, the evidence has conflicting results that would support atherosclerosis as the underlying pathology. Actually, other nonatherosclerotic mechanisms related to connective tissue remodeling may play a role. Such mechanism is supported by epidemiological evidence that cCA DE is associated with carotid dissections. Similarly, cCA DE has been associated with vascular risk factors, but inconsistently. Fewer studies have evaluated the risk of vascular events in people with cCA DE. Cross-sectionally, cCA DE is associated with cerebrovascular disease, including white matter hyperintensities, lacunar stroke, and stroke overall. The often-conflicting results may in part be due to the heterogeneity of the population studies and variable definitions used. Preferential use of objective measure of cCA DE, such as carotid length, is advisable, and may help comparing result among different studies. Prospectively, people with cCA DE have a higher risk of vascular events, although it is uncertain if the risk of stroke is also higher in this population. In the absence of alternative stroke etiologies, stroke patients with cCA DE should be considered to have had a cryptogenic stroke and treated with daily antiplatelet therapy. Further population-based studies are needed to clarify whether specific therapies may be implement to reduce the risk of events among people with cCA DE.

Editors' note: The dimension of preventable stroke in a large representative patient cohort

In spite of the considerable benefits to interventions for modifiable vascular disease risk factors, evidence indicates most ischemic strokes continue to be associated with poorly controlled lifestyle behaviors and medical conditions. In their nested cohort study of the Post-Stroke Disease Management STROKE-CARD trial, Drs. Boehme et al. found that 4 out of 5 patients with ischemic stroke had at least 1 inadequately managed lifestyle behavior or vascular comorbidity. Surprisingly, patients who had a prior stroke were even more likely to have 1 inadequately managed risk factor—which the authors attribute to the more extensive recommendations for secondary stroke prevention (e.g., antithrombotic and statin use) when compared to primary prevention. While the study highlights the failure of primary prevention strategies across stroke patients, it was limited in that only 8 risk factors were assessed. As Dr. Kelly indicates, chronic kidney disease (CKD) is one important vascular risk factor that was not addressed in this study. While CKD may not necessarily be a modifiable risk factor (in the sense that hypertension and body mass index may be modifiable), the presence of CKD may be a limiting factor for certain pharmacologic interventions for primary or secondary prevention. Using an admission glomerular filtration rate (GFR) cutoff of <60 mL/min/1.73 m2 as a threshold for CKD, the investigators subsequently reported no difference in the proportion of patients with at least one inadequately managed risk factor with or without CKD. Dr. Goldstein also responds to the investigators' comment that risk factor modification among diabetic patients has unclear benefits for stroke risk reduction. Dr. Goldstein emphasizes that these patients show a clear benefit if blood pressure and dyslipidemia are managed appropriately, and if antithrombotic use is initiated among diabetics at high risk of vascular events. The investigators then returned to their source data and found that diabetic patients—although representing only 9.9% of patients who were undertreated based on measures of glycemic control—were particularly undertreated for other comorbid vascular risk factors when compared to non-diabetic patients. This study adds to the growing literature that indicates a significant gap in practice-based recommendations and clinical practice when it comes to stroke prevention. In spite of the considerable benefits to interventions for modifiable vascular disease risk factors, evidence indicates most ischemic strokes continue to be associated with poorly controlled lifestyle behaviors and medical conditions. In their nested cohort study of the Post-Stroke Disease Management STROKE-CARD trial, Drs. Boehme et al. found that 4 out of 5 patients with ischemic stroke had at least 1 inadequately managed lifestyle behavior or vascular comorbidity. Surprisingly, patients who had a prior stroke were even more likely to have 1 inadequately managed risk factor—which the authors attribute to the more extensive recommendations for secondary stroke prevention (e.g., antithrombotic and statin use) when compared to primary prevention. While the study highlights the failure of primary prevention strategies across stroke patients, it was limited in that only 8 risk factors were assessed. As Dr. Kelly indicates, chronic kidney disease (CKD) is one important vascular risk factor that was not addressed in this study. While CKD may not necessarily be a modifiable risk factor (in the sense that hypertension and body mass index may be modifiable), the presence of CKD may be a limiting factor for certain pharmacologic interventions for primary or secondary prevention. Using an admission glomerular filtration rate (GFR) cutoff of <60 mL/min/1.73 m2 as a threshold for CKD, the investigators subsequently reported no difference in the proportion of patients with at least one inadequately managed risk factor with or without CKD. Dr. Goldstein also responds to the investigators' comment that risk factor modification among diabetic patients has unclear benefits for stroke risk reduction. Dr. Goldstein emphasizes that these patients show a clear benefit if blood pressure and dyslipidemia are managed appropriately, and if antithrombotic use is initiated among diabetics at high risk of vascular events. The investigators then returned to their source data and found that diabetic patients—although representing only 9.9% of patients who were undertreated based on measures of glycemic control—were particularly undertreated for other comorbid vascular risk factors when compared to non-diabetic patients. This study adds to the growing literature that indicates a significant gap in practice-based recommendations and clinical practice when it comes to stroke prevention.

Impact of Dissection after Drug-Coated Balloon Treatment of De Novo Coronary Lesions: Angiographic and Clinical Outcomes.

PurposeDissection after plain balloon angioplasty is required to achieve adequate luminal area; however, it is associated with a high risk of vascular events. This study aimed to examine the relationship between non-flow limiting coronary dissections and subsequent lumen loss and long-term clinical outcomes following successful drug-coated balloon (DCB) treatment of de novo coronary lesions.Materials and MethodsA total of 227 patients with good distal flow (Thrombolysis in Myocardial Infarction flow grade 3) following DCB treatment were retrospectively enrolled and stratified according to the presence or absence of a non-flow limiting dissection. The primary endpoint was late lumen loss (LLL) at 6-month angiography, and the secondary endpoint was target vessel failure (TVF, a composite of cardiac death, target vessel myocardial infarction, target vessel revascularization, and target vessel thrombosis).ResultsThe cohort consisted of 95 patients with and 132 patients without a dissection. There were no between-group differences in LLL (90.8%) returning for angiography at 6 months (0.05±0.19 mm in non-dissection and 0.05±0.30 mm in dissection group, p=0.886) or in TVF (6.8% in non-dissection and 8.4% in dissection group, p=0.799) at a median follow-up of 3.4 years. In a multivariate analysis, the presence of dissection and its severity were not associated with LLL or TVF. Almost dissections (93.9%) were completely healed, and there was no newly developed dissection at 6-month angiography.ConclusionThe presence of a dissection following successful DCB treatment of a de novo coronary lesion may not be associated with an increased risk of LLL or TVF (Impact of Drug-coated Balloon Treatment in de Novo Coronary Lesion; NCT04619277).

Epilepsy and vascular risk

Epidemiological studies have shown that mortality increases in patients with epilepsy compared to the general population, and this has been associated with an increased risk of cardiovascular or cerebrovascular events. The role played by classic and more speculative vascular risk factors (e.g. oxidative stress) in the development of vascular disease in these subjects has not yet been clearly established. In this context, antiepileptic drugs (AEDs) may have a differential influence on the vascular risk of patients with epilepsy, as enzyme inducers have been linked to the development of early atherosclerosis. The role of AEDs in the pathogenesis of atherosclerosis is not fully understood, but there are several plausible explanations: they can condition an unfavourable lipid profile, they can increase levels of C-reactive protein and homocysteinaemia, as well as clotting factors, and they can increase oxidative stress. Prolonged use of AEDs can be associated with a wide range of chronic adverse effects, and may also play a key role in the pathogenesis of atherosclerosis in patients with epilepsy. Neurologists and epileptologists who prescribe AEDs should be aware of the potentially unfavourable effects, especially in patients at high risk of vascular events. This review examines the pathophysiological mechanisms that may explain increased vascular risk in epilepsy, the evidence regarding accelerated atherosclerosis and its complications, and the potential implications for follow-up and treatment of the disease.

Clinical Relevance of Cerebral Small Vessel Diseases.

Clinical Relevance of Cerebral Small Vessel Diseases.

Current Medical and Surgical Stroke Prevention Therapies for Patients with Carotid Artery Stenosis.

Carotid Artery Stenosis (CAS) is a marker of systemic atherosclerosis and patients with CAS are at high risk of vascular events in multiple vascular locations, including ipsilateral ischemic stroke. Both medical and surgical therapies have been demonstrated effective in reducing this risk. The optimal management for patients with asymptomatic carotid artery stenosis remains controversial. In patients with symptomatic CAS ≥70%, CEA has been demonstrated to reduce the risk of stroke. With the risk of recurrent stroke being particularly high in the first 2 weeks after the first event, Carotid Endarterectomy (CEA) or carotid angioplasty with stenting provides maximal benefits to patients with symptomatic CAS ≥70% if performed within this «2-week» target. Several large ongoing trials are currently comparing the risks and benefits of carotid revascularization versus medical therapy alone.

Evaluation of inter-arm difference in blood pressure as predictor of vascular diseases among urban adults in Kancheepuram District of Tamil Nadu.

Introduction:An “Inter-Arm Difference” (IAD) in blood pressure (BP) is defined as a variation in systolic BP of >10 mmHg. Various studies conducted in different population show that there are wide variations in the prevalence of IAD, which ranges from 5% to 46%. The aim of this study is to evaluate the prevalence of IAD in BP among adults and its association with risk factors.Methods:This community-based cross-sectional study was carried out among urban adults in Kancheepuram district. The study sample size of 1634 was calculated, and simple random sampling method was used. Data analysis was performed using SPSS software version 16. Prevalence of IAD in BP was calculated using percentages, and statistical significance was tested to look for an association.Results:This study shows that 26.2% were at moderate risk for vascular events with IAD in systolic BP of 10–15 mmHg and 17.3% were at high risk with IAD >15 mmHg. About 14.2% had diastolic BP difference of 10–15 mmHg indicative of moderate risk and 6.1% had a difference of >15 mmHg indicative of high risk for vascular events. The statistical significant association was found between IAD in systolic BP and risk factors such as hypertension, smoking, alcoholism, and between IAD in diastolic BP with overweight/obesity (P < 0.05).Conclusion:This study outcome shows that the prevalence of IAD in BP is on the higher side. Hence, specific guidelines should be brought in to practice for measuring BP in both arms to detect IAD in every health-care settings.

Inter-arm systolic blood pressure differences, relations with future vascular events and mortality in patients with and without manifest vascular disease

BackgroundInter-arm systolic blood pressure difference (SBPD) is an easily obtained patient characteristic which relates to vascular disease. We aimed to identify determinants of large inter-arm SBPD and to investigate the relation between inter-arm SBPD and vascular events in patients with and without manifest vascular disease. MethodsIn a cohort of 7344 patients with manifest vascular disease or vascular risk factors alone enrolled in the Second Manifestations of ARTerial disease (SMART) study, single bilateral non-simultaneous blood pressure measurements were performed. Logistic and Cox regression was used to identify determinants of large inter-arm SBPD (≥15mmHg) and to investigate the relation between inter-arm SBPD and vascular events (composite of non-fatal myocardial infarction, stroke, and vascular mortality) and all-cause mortality. ResultsIn all patients the median inter-arm SBPD was 7mmHg (IQR 3–11) and 1182 (16%) patients had inter-arm SBPD ≥15mmHg. Higher age, higher systolic blood pressure, diabetes mellitus, peripheral artery disease, carotid artery stenosis, higher carotid intima-media thickness, and lower ankle-brachial indices were related to large inter-arm SBPD (≥15mmHg). Each 5mmHg increase in inter-arm SBPD was related to a 12% higher risk of vascular events in patients without manifest vascular disease (HR 1.12; 95% CI 1.00–1.27), whereas no relation was apparent in patients with manifest vascular disease (HR 0.98; 95% CI 0.93–1.04, interaction p-value 0.036). Inter-arm SBPD was not related to all-cause mortality (HR 1.05; 95% CI 0.93–1.19). ConclusionsInter-arm SBPD relates to a higher risk of vascular events in patients without manifest vascular disease, whereas this relation is not apparent in patients with manifest vascular disease.

Retinal artery occlusion and associated recurrent vascular risk with underlying etiologies.

Background and purposeRAO is caused by various etiologies and subsequent vascular events may be associated with underlying etiologies. Our aim is to investigate the etiologies of RAO, the occurrence of subsequent vascular events and their association in patients with RAO.MethodsWe analyzed data from 151 consecutive patients presenting with acute non-arteritic RAO between 2003 and 2013 in a single tertiary-care hospital. The primary outcome was the occurrence of a vascular event defined as stroke, myocardial infarction, and vascular death within 365 days of the RAO onset. The Kaplan-Meier survival analysis and Cox proportional hazard model were used to estimate the hazard ratio of the vascular events.ResultsLarge artery atherosclerosis (LAA) was the etiology more frequently associated with of RAO (41.1%, 62/151). During the one year follow-up, ischemic stroke and vascular events occurred in 8.6% and 9.9% of patients, respectively. Ten vascular events occurred in RAO patients attributed to LAA and 4 occurred in undetermined etiology. RAO patients with LAA had a nearly four times higher risk of vascular events compared to those without LAA (hazard ratio 3.94, 95% confidence interval 1.21–12.81). More than a half of all events occurred within one month and over three fourths of ischemic strokes occurred ipsilateral to the RAO.ConclusionAfter occurrence of RAO, there is a high risk of a subsequent vascular event, particularly ipsilateral stroke, within one month. LAA is an independent factor for the occurrence of a subsequent vascular event. Management for the prevention of secondary vascular events is necessary in patients with RAO especially with LAA. Large clinical trials are needed to confirm these findings.

The BCR/ABL tyrosine kinase inhibitor, nilotinib, stimulates expression of IL-1β in vascular endothelium in association with downregulation of miR-3p

BCR/ABL tyrosine kinase inhibitors (TKIs) have significantly improved the prognosis for in dividuals with chronic myeloid leukemia (CML). However, many patients treated with TKIs suffer from TKI-related complications. In particular, vascular events such as peripheral artery occlusive disease have become aserious clinical problem for patients who receive the TKI, nilotinib. At present, the molecular mechanisms by which TKIs cause vascular endothelial cell insults remain unknown.This study explored the effects of the TKIs, imatinib, nilotinib and dasatinib, on vascular endothelial cells in vitro, and found that only nilotinib induced expression of interleukin-1β (IL-1β) by vascular endothelial cells. Nilotinib-induced IL-1β expression stimulated the adhesion of monocytes to vascular endothelial cells in association with an increase in levels of adhesion molecules. MicroRNA database searching identified miR-3121-3p binding sites in the 3′-UTR of the IL-1β gene. Exposure of endothelial cells to nilotinib caused downregulation of miR-3121-3p in these cells. Importantly, forced-expression of miR-3121-3p counteracted nilotinib-induced expression of IL-1β. Importantly, serum levels if IL-1β were significantly elevated in CML patients receiving nilotinib (n=14) compared to those receiving other TKIs (n=16) (3.76±1.22pg/ml vs 0.27±0.77pg/ml, p<0.05). Taken together, our data suggest that nilotinib decreases levels of miR-3121-3p resulting in an increase in expression of IL-1β and adhesion molecules in vascular endothelial cells. The miR-3121-3p/IL-1β axis could be a potential target to prevent vascular events in CML patients with high risk of vascular events.

Vascular parkinsonism and vascular dementia are associated with an increased risk of vascular events or death.

IntroductionThe natural course of vascular parkinsonism (VaP) and dementia (VaD) due to cerebral small vessel disease (SVD) is not well known. The aim of this single-center study was to evaluate the long-term risk of vascular events, death and dependency in patients with VaP or VaD and to compare it with patients without cerebrovascular disease but with high atherothrombotic risk.Material and methodsSeventy-eight consecutive, functionally independent patients with MRI features of SVD and with recently diagnosed VaD (n = 50) and VaP (n = 28) and 55 controls (control group – CG) with high 10-year risk of total cardiovascular disease (SCORE ≥ 5%) were prospectively recruited and followed for 24 months.ResultsPatients with SVD had lower prevalence of coronary artery disease compared with the CG (20.5% vs. 40%; p = 0.02) but similar prevalence of other atherothrombotic risk factors including mean age (73.7 ±7.3 vs. 72 ±5.9 years, p = 0.09). All outcomes were worse in SVD patients than controls. Thirty-one percent of SVD patients (34% of VaD vs. 25% of VaP, p = 0.45) experienced vascular events or died compared to 6% of controls (p < 0.01). After adjustments for potential confounders (age, sex, vascular risk factors), patients with VaP (HR = 7.5; 95% CI: 1.6–33; p < 0.01) and VaD (HR = 8.7; 95% CI: 2.1–35; p < 0.01) had higher risk of vascular events or death and death or dependency (respectively; HR = 3.9; 95% CI: 0.83–18.8; p = 0.07 and HR = 4.7, 95% CI: 1.1–19.7; p = 0.03).ConclusionsPatients with VaP or VaD due to SVD had significantly higher risk of vascular events, death and dependency compared to controls with high cardiovascular risk and without cerebrovascular disease.

Impact of Educational Attainment on Health Outcomes in Moderate to Severe CKD

BackgroundThe inverse association between educational attainment and mortality is well established, but its relevance to vascular events and renal progression in a population with chronic kidney disease (CKD) is less clear. This study aims to determine the association between highest educational attainment and risk of vascular events, cause-specific mortality, and CKD progression.Study DesignProspective epidemiologic analysis among participants in the Study of Heart and Renal Protection (SHARP), a randomized controlled trial.Setting & Participants9,270 adults with moderate to severe CKD (6,245 not receiving dialysis at baseline) and no history of myocardial infarction or coronary revascularization recruited in Europe, North America, Asia, Australia, and New Zealand.PredictorHighest educational attainment measured at study entry using 6 levels that ranged from “no formal education” to “tertiary education.”OutcomesAny vascular event (any fatal or nonfatal cardiac, cerebrovascular, or peripheral vascular event), cause-specific mortality, and CKD progression during 4.9 years’ median follow-up.ResultsThere was a significant trend (P < 0.001) toward increased vascular risk with decreasing levels of education. Participants with no formal education were at a 46% higher risk of vascular events (relative risk [RR], 1.46; 95% CI, 1.14-1.86) compared with participants with tertiary education. The trend for mortality across education levels was also significant (P < 0.001): all-cause mortality was twice as high among those with no formal education compared with tertiary-educated individuals (RR, 2.05; 95% CI, 1.62-2.58), and significant increases were seen for both vascular (RR, 1.84; 95% CI, 1.21-2.81) and nonvascular (RR, 2.15; 95% CI, 1.60-2.89) deaths. Lifestyle factors and prior disease explain most of the excess mortality risk. Among 6,245 participants not receiving dialysis at baseline, education level was not significantly associated with progression to end-stage renal disease or doubling of creatinine level (P for trend = 0.4).LimitationsNo data for employment or health insurance coverage.ConclusionsLower educational attainment is associated with increased risk of adverse health outcomes in individuals with CKD.